Antigen Presenting Cells (APCs) play a role in the complex response of the immune system. For example, pathogen recognition receptors are present on APCs and serve to recognize a foreign antigen to the human body, bind to that antigen and present that antigen to lymphocytes to induce antigen-specific lymphocytes to produce protective immunity. Pathogen recognition receptors are essential for APCs to present antigens to lymphocytes to induce them to produce adaptive immunity—(a) humoral immunity in the form of production of antibodies and (b) cell-mediated immunity, e.g. the production of cytotoxic T lymphocytes, activated macrophages, activated natural killer cells, cytokines, and the like.
A1 adenosine receptors are pathogen recognition receptors. It has been reported that lipopolysaccharide binds to A1 adenosine receptors. Wilson, C N and Batra V K, J Endotoxin Research 8:263-271, (2002). Moreover, A1 adenosine receptors are present on human dendritic cells, monocytes, macrophages, lymphocytes and peripheral blood mononuclear cells. Panther, E, et al FASEB J 15: 1963, (2001); Salmon J E, J Immunol 151:2775, (1993); Marone G, Int J Clin Lab Res 22:235, (1992); Marone G, Int Arch Allergy Appl Immunol 77:259, 1985; Mayne M, Ann Neurol 45:633, 1999). Additionally, treatment of immature human dendritic cells in vitro with adenosine does alter expression of cell surface markers considered important for dendritic cell function. Panther E, Blood 101:3985, (2003). Panther et al. have published research that suggests adenosine “may control proinflammatory activities of DC's and regulate their accumulation at target sites” (Panther et al. (2001)), but also published a study concluding that the A2 adenosine receptor is responsible for the phenotypic changes in dendritic cell function. Panther et al. Blood 101(10): 3985-3990 (2003).
In spite of the foregoing, a potential relationship between immune deficiency and deficient A1 adenosine receptor function has not been previously examined outside the area of multiple sclerosis where it has been reported that A1 adenosine receptor expression is reduced in monocytes/macrophages in blood and brains of patients with multiple sclerosis. Johnston J B, Ann Neurol 49:650 (2001); Mayne M, Ann Neurol 45:633 (1999).